ATMOXIDE-H Tablets

Composition
  • Each Tablet Contains:
  • Amitriptyline
    12.5 mg
  • Chlordiazepoxide
    5 mg

Packing
  • 10x10
    (Alu-Strip)
MRP
  • 22

Overview

Amitriptyline belongs to a group of medicines called tricyclic antidepressants. Serotonin and noradrenaline are neurotransmitters chemicals that relay signals between the cells in your brain.TCAs increase the amount of these two neurotransmitters in your brain, and this is how amitriptyline is thought to improve the symptoms of depression.
Chlordiazepoxide is used for the treatment of anxiety. It is a member of the benzodiazepine family of compounds, which slow the central nervous system in order to ease tension or nervousness. Chlordiazepoxide is used for the short-term relief of symptoms of anxiety and management of anxiety disorders. It is also used for treating symptoms of withdrawal from acute alcoholism and alcoholic intoxication.

Contraindications

Chlordiazepoxide amitriptyline ds tablets is contraindicated in patients with hypersensitivity to either benzodiazepines or tricyclic antidepressants. It should not be given concomitantly with a monoamine oxidase inhibitor. Hyperpyretic crises, severe convulsions and deaths have occurred in patients receiving a tricyclic antidepressant and a monoamine oxidase inhibitor simultaneously.

Dosage

This is Preferred Dosage:

  • As directed by physician.
  • Optimum dosage varies with the severity of the symptoms and the response of the individual patient. When a satisfactory response is obtained, dosage should be reduced to the smallest amount needed to maintain the remission. The larger portion of the total daily dose may be taken at bedtime. In some patients, a single dose at bedtime may be sufficient. In general, lower dosages are recommended for elderly patients.
  • Chlordiazepoxide amitriptyline as tablets are recommended in an initial dosage of 3 or 4 tablets daily in divided doses; this may be increased to 6 tablets daily as required. Some patients respond to smaller doses and can be maintained on 2 tablets daily.
Disclaimer:To be taken only after consulting with the doctor.

Pharmacology

Mechanism of Action

Amritiptyline:
Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on thedopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin. It is metabolised to nortriptyline-a more potent and selective norepinephrine reuptake inhibitor which may complement its effects on norepinephrine reuptake.
Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2, H4, and receptor antagonist, and σ1 receptor agonist. It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well. Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors. It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models. These are the same receptors BDNF activates, an endogenousneurotrophin with powerful antidepressant effects, and as such this property may contribute significantly to its therapeutic efficacy against depression. Amitriptyline also acts as a functional inhibitor of acid sphingomyelinase.

Chlordiazepoxide:
Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, diazepam, clonazepam,oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam. Clorazepate is a long-acting benzodiazepine drug. Clorazepate produces the active metabolite desmethyl-diazepam, which is a partial agonist of the GABAA receptor and has a half life of 20-179 hours; a small amount of desmethyldiazepam is further metabolised into oxazepam. Clorazepate exerts its pharmacological properties via increasing the opening frequency of the chloride ion channel of GABAA receptors. This effect of benzodiazepines requires the presence of the neurotransmitter GABA and results in enhanced inhibitory effects of the neurotransmitter GABA acting on GABAAreceptors. Clorazepate, like other benzodiazepines, is widely distributed and is highly bound to plasma proteins; clorazepate also crosses readily over the placenta and into breast milk. Peak plasma levels of the active metabolite desmethyl-diazepam are seen between 30 minutes and 2 hours after oral administration of clorazepate. Clorazepate is completely metabolised to desmethyl-diazepam in the gastrointestinal tract and thus the pharmacological properties of clorazepate are largely due to desmethyldiazepam.

Chemistry

Amitriptyline is the most widely used tricyclic antidepressant. Amitriptyline is chemically basic and is in the form of hydrochloride salt in the market. It is used to treat a number ofmental disorders, including major, depressive disorder and anxiety, and less commonly psychosis, attention deficit hyperactivity disorder, and bipolar disorder. Other uses include prevention of migraines, postherpetic neuralgia, neuropathic pain such asfibromyalgia, and less commonly insomnia.

STRUCTURE OF AMITRITPTYLINE

3-(10,11-Dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine
Chlordiazepoxide is a sedative/hypnotic drug and benzodiazepine. Chlordiazepoxide was the first benzodiazepine to be synthesized and the discovery of chlordiazepoxide was by pure chance. Chlordiazepoxide and other benzodiazepines were initially accepted with widespread public approval but were followed with widespread public disapproval and recommendations for more restrictive medical guidelines for its use.

STRCUCTURE OF CHLORDIAZEPOXIDE




7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide

Clinical Data

Clinical Data of Amitriptyline

Pregnancy category
AU: C
US: C
Legal status
AU: Prescription Only (S4)
CA: Rx-only
UK: POM
US: Rx-only
Routes
Oral

Chemical Data

Pregnancy Formula

C20H23N
Molecular mass

277.403 g/mol



Clinical Data of Chlordiazepoxide

Pregnancy category
US: D
Legal status
AU: Prescription Only (S4)
UK: POM
US: Schedule IV
Routes
oral
intramuscular

Chemical Data

Pregnancy Formula

C16H14ClN3O
Molecular mass

299.75 g/mol